SUMMARY:Ipilimumab is a promising new immunotherapeutic antineoplastic agent with clinical activity in the treatment of metastatic melanoma and renal cell carcinoma. With advances in immunotherapy, however, a host of new side effects related to the mechanism of action of these drugs has appeared. At our institution, 3 patients presented with hypophysitis, which was attributed to an autoimmune process based on the documented relationship of the drug to other autoimmune phenomena and significant and rapid improvement with discontinuation of the drug and addition of steroids. We present the imaging findings in 3 patients with presumed ipilimumab-induced hypophysitis.
Ipilimumab, also known as MDX-010, is a human monoclonal antibody that has been shown to overcome the suppressive effects of cytotoxic T-lymphocyte antigen 4 expression, thereby enhancing the immune response against tumors. 1 This drug has been shown in trials to have clinical activity against metastatic melanoma.2 Side effects are related to its mechanism of action, including development of immune-related adverse events such as hypophysitis, colitis, uveitis, dermatitis, and arthritis, among others. 3 We describe 3 cases in which patients treated with ipilimumab developed both MR imaging and clinical findings characteristic of hypophysitis. We will describe these findings and provide a brief discussion of the causes and imaging characteristics of hypophysitis.
Case Reports
Case 1Patient 1 was a 70-year-old man originally diagnosed with a Clark level IV melanoma of the right shoulder, and later found to have cervical nodal metastasis. He was enrolled in an ipilimumab study and received 3 doses of antibody at 10 mg/kg for 6 weeks. Shortly after his third dose, he presented with complaints of visual hallucinations, lack of energy, dizziness on erect position, and anorexia. MR imaging revealed no evidence of metastatic disease but instead showed enlargement of the pituitary gland from the original baseline (from 5 mm craniocaudally to 12 mm). Laboratory studies disclosed the following values: a total T4 of 3.6 g/dL (normal, 5.5-11.0 g/dL) and a drop in adrenocorticotropic hormone (ACTH) from 21 to 9 pg/mL, thyroidstimulating hormone (TSH) from 1.99 to 0.005 L, and cortisol from 9.04 to 2.31 g/dL compared with laboratory values obtained before initiation of therapy. He also had a total testosterone level Ͻ20 ng/dL with a decrease in luteinizing hormone and follicle-stimulating hormone (FSH). He received tapering doses of prednisone starting at 60 mg daily as well as levothyroxine (Synthroid) 50 mcg daily. Follow-up laboratory values and imaging showed improvement for several weeks following discontinuation of ipilimumab, along with corresponding improvement in symptoms on replacement therapy (Fig 1).
Case 2Patient 2 was a 44-year-old man with stage IV desmoplastic neurotropic melanoma found in the lower lip. He initially underwent excision and radiation therapy but was later found to have neurotropic spread along the maxillary division of the trigeminal ne...
Background: Adrenal lesions are commonly identifi ed in patients with extra-adrenal cancer. When lesions are present, it is important to identify if the lesion is a metastasis of the
The treatment with TMZ is effective and safe in patients with aggressive corticotrophin tumors resistant to conventional therapy. Nevertheless once the disease progresses, a second course of treatment does not seem to be effective.
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